Memantyna w łagodnych zaburzeniach poznawczych i otępieniu alzheimerowskim o nasileniu lekkim: przesłanki teoretyczne, badania kliniczne i rekomendacje stosowania

• Authors: Tomasz Sobów

Title variants

EN

Memantine in mild cognitive impairment and mild dementia of Alzheimer’s disease: theoretical background, clinical trials and recommendations

• Languages of publication: EN PL

Abstracts

EN

Memantine, uncompetitive antagonist of NMDA receptor, is currently registered worldwide for the treatment of moderate to advanced dementia in the course of Alzheimer’s disease and is used either in monotherapy or in combination with cholinesterase inhibitor. Memantine’s efficacy has been documented in several clinical trials within cognition, behaviour and activities of daily living domains; the more advanced dementia the bigger effect size is usually seen. Adding memantine to an ongoing cholinesterase inhibitors exerts augmentation. Memantine efficacy in less advanced stages of Alzheimer’s dementia is the matter of controversy. It is highly unlikely to see an evident clinical benefit in the group of patients with initial MMSE above 20. Early treatment with memantine is thought to exert long-term consequences as probable disease-modifying effect may come to action. Data supporting this view (and, as a result, early treatment with memantine) is mainly of clinical nature and need to be confirmed with the use of validated disease progression biomarkers. Patients with mild dementia of Alzheimer’s type may be rationally treated with memantine monotherapy, even considering probable lack of symptomatic effect, when cholinesterase inhibitors are contraindicated or poorly tolerated. Data supporting the use of memantine in mild cognitive impairment are currently insufficient.

PL

Memantyna, niekompetycyjny antagonista receptora NMDA, jest obecnie zarejestrowana do leczenia choroby Alzheimera, w otępieniu o nasileniu umiarkowanym do znacznego, w monoterapii lub połączeniu z inhibitorem cholinesterazy. Badania kliniczne udokumentowały jej skuteczność w zakresie funkcji poznawczych, zachowania oraz codziennego funkcjonowania. Efekt kliniczny jest zwykle tym bardziej widoczny, im większe jest nasilenie otępienia. Dodanie memantyny do uprzednio stosowanego inhibitora cholinesterazy wzmacnia efekt objawowy. Skuteczność memantyny w mniej nasilonych stadiach otępienia stanowi przedmiot kontrowersji. Dostępne dane kliniczne sugerują brak widocznego efektu objawowego u większości pacjentów z wyjściowym MMSE >20. Wczesne włączenie leku może mieć długoterminowe konsekwencje w postaci modyfikacji naturalnej progresji dysfunkcji poznawczych. Dostępne dane wspierające taki pogląd (i wczesne stosowanie memantyny) oparte są jednak tylko na badaniach klinicznych i wymagają potwierdzenia w analizach z wykorzystaniem neurobiologicznych markerów choroby Alzheimera. Niewątpliwie racjonalne, pomimo prawdopodobnie niewielkiego wpływu objawowego, jest włączenie memantyny u chorych z lekkim otępieniem, którzy nie mogą być leczeni inhibitorem cholinesterazy. Przesłanki, aby stosować memantynę w stadium łagodnych zaburzeń poznawczych, należy obecnie uznać za niewystarczające.

Keywords

EN

Alzheimer’s disease; choroba Alzheimera; dementia; leczenie; memantine; memantyna; mild cognitive impairment; otępienie; treatment; łagodne zaburzenia poznawcze

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Aktualności Neurologiczne
• Year: 2014
• Volume: 14
• Issue: 1
• Pages: 54-60

Contributors

author

Tomasz Sobów

• Zakład Psychologii Lekarskiej, Uniwersytet Medyczny w Łodzi. Centralny Szpital Kliniczny, Uniwersytet Medyczny w Łodzi, ul. Czechosłowacka 8/10, 92-216 Łódź,

References

• 1. O’Brien J.T., Burns A.; BAP Dementia Consensus Group: Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology. J. Psychopharmacol. 2011; 25: 997–1019.
• 2. Bond M., Rogers G., Peters J. i wsp.: The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease (review of Technology Appraisal No. 111): a systematic review and economic model. Health Technol. Assess. 2012; 16: 1–470.
• 3. Tan C.C., Yu J.T., Wang H.F. i wsp.: Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. J. Alzheimers Dis. 2014; 41: 615-631.
• 4. Sobow T.: Combination treatments in Alzheimer’s disease: risks and benefits. Expert Rev. Neurother. 2010; 10: 693-702.
• 5. Riordan K.C., Hoffman Snyder C.R., Wellik K.E. i wsp.: Effectiveness of adding memantine to an Alzheimer dementia treatment regimen which already includes stable donepezil therapy: a critically appraised topic. Neurologist 2011; 17: 121-123.
• 6. Gauthier S., Molinuevo J.L.: Benefits of combined cholines-terase inhibitor and memantine treatment in moderate-severe Alzheimer’s disease. Alzheimers Dement. 2013; 9: 326-331.
• 7. Di Santo S.G., Prinelli F., Adorni F. i wsp.: A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine and memantine in relation to severity of Alzheimer’s disease. J. Alzheimers Dis. 2013; 35: 349-361.
• 8. McClendon M.J., Hernandez S., Smyth K.A., Lerner A.J.: Memantine and acetylcholinesterase inhibitor treatment in cases of CDR 0.5 or questionable impairment. J. Alzheimers Dis. 2009; 16: 577-583.
• 9. Schneider L.S., Insel P.S., Weiner M.W: Treatment with cholin-esterase inhibitors and memantine of patients in the Alzheimer’s Disease Neuroimaging Initiative. Arch. Neurol. 2011; 68: 58-66.
• 10. Petersen R.C., Caracciolo B., Brayne C. i wsp.: Mild cognitive impairment: a concept in evolution. J. Intern. Med. 2014; 275: 214-228.
• 11. Zorumski C.F., Izumi Y.: NMDA receptors and metaplasticity: mechanisms and possible roles in neuropsychiatric disorders. Neurosci. Biobehav. Rev. 2012; 36: 989-1000.
• 12. Morris R.G.: NMDA receptors and memory encoding. Neuropharmacology 2013; 74: 32-40.
• 13. Mukherjee S., Manahan-Vaughan D.: Role of metabotropic glutamate receptors in persistent forms of hippocampal plasticity and learning. Neuropharmacology 2013; 66: 65-81.
• 14. Danysz W, Parsons C.G.: The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: preclinical evidence. Int. J. Geri-atr. Psychiatry 2003; 18 (supl. 1): S23-S32.
• 15. Lipton S.A.: Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat. Rev. Drug Discov. 2006; 5: 160-170.
• 16. Francis P.T.: Glutamatergic systems in Alzheimer’s disease. Int. J. Geriatr. Psychiatry 2003; 18 (supl. 1): S15-S21.
• 17. Bell K.F., Bennett D.A., Cuello A.C.: Paradoxical upregulation of glutamatergic presynaptic boutons during mild cognitive impairment. J. Neurosci. 2007; 27: 10810-10817.
• 18. Esposito Z., Belli L., Toniolo S. i wsp.: Amyloid β, glutamate, excitotoxicity in Alzheimer’s disease: are we on the right track? CNS Neurosci. Ther. 2013; 19: 549-555.
• 19. Revett T.J., Baker G.B., Jhamandas J., Kar S.: Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology. J. Psychiatry Neurosci. 2013; 38: 6-23.
• 20. Greenamyre J.T, Maragos W.F., Albin R.L. i wsp.: Glutamate transmission and toxicity in Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 1988; 12: 421-430.
• 21. Lipton S.A.: Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx 2004; 1: 101-110.
• 22. Chen H.S., Lipton S.A.: The chemical biology of clinically tolerated NMDA receptor antagonists. J. Neurochem. 2006; 97: 1611-1626.
• 23. Reisberg B., Doody R., Stöffler A. i wsp.: Memantine in moderate-to-severe Alzheimer’s disease. N. Engl. J. Med. 2003; 348: 1333-1341.
• 24. van Dyck C.H., Tariot P.N., Meyers B., Malca Resnick E.; Memantine MEM-MD-01 Study Group: A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis. Assoc. Disord. 2007; 21: 136-143.
• 25. Tariot P.N., Farlow M.R., Grossberg G.T. i wsp.: Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004; 291: 317-324.
• 26. Winblad B., Poritis N.: Memantine in severe dementia: results of the 9M-Best Study. Int. J. Geriatr. Psychiatry 1999; 14: 135-146.
• 27. Winblad B., Jones R.W., Wirth Y. i wsp.: Memantine in moderate to severe Alzheimer’s disease: a meta-analysis of randomized clinical trials. Dement. Geriatr. Cogn. Disord. 2007; 24: 20-27.
• 28. Rive B., Gauthier S., Costello S. i wsp.: Synthesis and comparison of the meta-analyses evaluating the efficacy of memantine in moderate to severe stages of Alzheimer’s disease. CNS Drugs 2013; 27: 573-582.
• 29. Tariot P.N., Farlow M.R., Grossberg G.T i wsp.: Memantine treatment in patients with moderate to severe Alzheimer’s disease already receiving donepezil: a randomized controlled trial. JAMA 2004; 291: 317-324.
• 30. Muayqil T., Camicioli R.: Systematic review and meta-analysis of combination therapy with cholinesterase inhibitors and memantine in Alzheimer’s disease and other dementias. Dement. Geriatr. Cogn. Dis. Extra 2012; 2: 546-572.
• 31. Peskind E.R., Potkin S.G., Pomara N. i wsp.: Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Am. J. Geriatr. Psychiatry 2006; 14: 704-715.
• 32. Porsteinsson A.P., Grossberg G.T., Mintzer J., Olin J.T.; Memantine MEM-MD-12 Study Group: Memantine treatment in patients with mild to moderate Alzheimer’s disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo- controlled trial. Curr. Alzheimer Res. 2008; 5: 83-89.
• 33. Bakchine S., Loft H.: Memantine treatment in patients with mild to moderate Alzheimer’s disease: results of a randomised, double-blind, placebo-controlled 6-month study. J. Alzheimers Dis. 2007; 11: 471-479.
• 34. Doody R.S., Tariot P.N., Pfeiffer E. i wsp.: Meta-analysis of six-month memantine trials in Alzheimer’s disease. Alzhei-mers Dement. 2007; 3: 7-17.
• 35. Schneider L.S., Dagerman K.S., Higgins J.P. i wsp.: Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch. Neurol. 2011; 68: 991-998.
• 36. Tricco A.C., Soobiah C., Berliner S. i wsp.: Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis. CMAJ 2013; 185: 1393-1401.
• 37. Cooper C., Li R., Lyketsos C., Livingston G.: Treatment for mild cognitive impairment: systematic review. Br. J. Psychiatry 2013; 203: 255-264.
• 38. Ferris S., Schneider L., Farmer K. i wsp.: A double-blind, placebo-controlled trial of memantine in age-associated memory impairment (memantine in AAMI). Int. J. Geriatr. Psychiatry 2007; 22: 448-455.
• 39. Lopez O.L., Becker J.T., Wahed A.S. i wsp.: Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry 2009; 80: 600-607. Erratum in: J. Neurol. Neurosurg. Psychiatry 2009; 80: 1056.
• 40. Atri A., Shaughnessy L.W, Locascio J.J., Growdon J.H.: Longterm course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis. Assoc. Disord. 2008; 22: 209-221.
• 41. Rountree S.D., Atri A., Lopez O.L., Doody R.S.: Effectiveness of antidementia drugs in delaying Alzheimer’s disease progression. Alzheimers Dement. 2013; 9: 338-345.
• 42. Zhu C.W, Livote E.E., Scarmeas N. i wsp.: Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer’s disease. Alzheimers Dement. 2013; 9: 733-740.
• 43. Stubendorff K., Larsson V, Ballard C. i wsp.: Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson’s disease with dementia: a prospective study. BMJ Open 2014; 4: e005158.
• 44. Dysken M.W, Sano M., Asthana S. i wsp.: Effect of vitamin E and memantine on functional decline in Alzheimer disease; the TEAM-AD VA cooperative randomized trial. JAMA 2014; 311: 33-44.

• Document Type: article